Regioselective alkylation of polysubstituted imidazoles is of importance especially with regard to Angiotensin II antagonists. The mechanisms of selective alkylation are somewhat understood and can be used in some circumstances to control reaction products, i.e. the distribution of N-alkylated regioisomeric products. However, no generally applicable methods currently exist for the regioselective alkylation of these important imidazoles in quantitative yield. The product by prior art methods is usually a mixture of regioisomers as shown in Scheme 1. ##STR1##
German Patent DE 2354786, Galenika Pharm Chem Ind., describes a nitration of an alkylimidazole to form the same general class of compounds as in the present invention. The isomers are separated by pH control so that the stronger base is protonated and stays in solution and the weaker, presumably non protonated, base is precipitated. The stronger base is isolated at pH 9. The desired N-alkylated imidazole is not isolated by salt formation/crystallization.
It is apparent, as determined by the nonquantitative formation of either regioisomer during N-alkylation, and the lack of suitable methods for the large scale purification of N-alkylated imidazoles that a method of purifying these very important compounds to obtain pure products from alkylation is needed when suitable crystallization is not an option because of the physical form, e.g. when product mixture is an oil